Background: Dasatinib treatment leads to excellent molecular responses in chronic phase chronic myeloid leukemia (CP-CML) but at 100mg leads to a substantial risk of pleural effusions, which may be higher in the elderly. Rousselot et al (BJH 2021) suggested this risk may be mitigated through dose modifications as guided by trough levels (Cmin). Aims: The CML12 (DIRECT) study, run by the ALLG, is a single arm phase II study, aiming to minimise dasatinib related toxicity whilst preserving efficacy, through dose adaptation as guided by dasatinib trough levels. We report here the primary end point - cumulative incidence of pleural effusion (PEf) at 24 months (mos) and key efficacy secondary end points. Methods: DIRECT enrolled newly diagnosed CP-CML pts. The first 34 patients (pts) were aged >60 years (yrs), after which the protocol was amended to include pts aged >18 yrs at the recommendation of the trial management committee. All pts started on dasatinib 100mg QD, with Cmin taken at 7, 28, 56 & 90 days, then every 3 mos hence. Pts sequentially dose reduced to 70mg, then to 50mg QD, for Cmin >3nM, within the first 2 mos, prior to assessment of early molecular response at 3 mos. Doses <50mg QD were permitted temporarily only for toxicity management. Chest x-ray and transthoracic echocardiograms were performed at baseline & 24 mos. Results: Eighty pts were enrolled from 14 centres, with a median follow up of 36 mos (range 24-60). Median age was 64 yrs (range 21-86) and 46% were female. The ELTS score was low and intermediate in 54% and 34% respectively, high in 5% and missing in 8%. Cmin and treatment assigned at various timepoints are detailed in Table 1. Older patients had higher Cmin, particularly prior to dose adjustments. The majority of pts were dose reduced to 50mg QD. Fifteen cases of pleural effusion (PEf) occurred, 5 within the first mo, and 12 in total by 24 mos; 3 were asymptomatically detected on chest x-ray. The cumulative incidence of PEf by 24 mos was 15% overall (95% CI 8-25%, Fig 1); with values of 7.6%, 14.3% and 45.5% respectively in patients <60 yrs, 60-75 yrs and ≥75 yrs. The Cmin prior to the PEf was >3nM in 8/15 pts. At 24 mos, 59 (74%) of pts remained on dasatinib. Reasons for discontinuation were intolerance / adverse events (AE) (n=15, 19%); treatment failure (n=4, 5%); death (n=1, 1%) and consent withdrawn (n=1, 1%). AEs leading to discontinuation were PEf (n=6, 7.5%) pulmonary hypertension (n=4, 5%; 2 reported as SAEs), pericardial effusion (n=2, 2.5%) and cardiac failure (n=2, 2.5%). There were no cases of peripheral vascular disease or strokes. An early molecular response (BCR::ABL1 <10% IS at 3 mos) was achieved in 77 pts (96%). Cumulative incidence of MMR (<0.1%) by 12 and 24 mos were 75% (95% CI 66-84%) and 92% (95% CI 86-97%), respectively; MR4.5 by 24 and 48 mos were 48% (95% CI 38-60%) and 76% (95% CI 64-90%), respectively. No patient progressed to AP/BC on or off study. Three pts have died of non CML-related causes (infection n=2; biliary carcinoma n=1). Image:Summary/Conclusion: High rates of MMR/MR4.5 were achieved, despite significant dose reductions, according to target drug levels over the first 2 months. Toxicity profile was also broadly favourable. However, such adaptive approaches had limited capacity to influence early development of PEf. A strategy using lower starting doses, with escalation for failure to achieve molecular targets, may further minimise toxicity, especially in the elderly.

P055 Table 1 Association between CE/HD scope and dysplasia detection Abstracts A42 Gut 2021;70(Suppl 3):A1–A76 on S etem er 2, 2021 by gest. P rocted by coright. http/gut.bm jcom / G t: frst pulished as 10.113utjnl-2021-B A S L.63 on 17 S etem er 221. D ow nladed fom

Abstract Funding Acknowledgements Bristol-Myers Squibb Background Right sided cardiac catheter ablation has become an indispensable tool to treat supraventricular cardiac dysrhythmias, with ablation of certain arrhythmias having cure rates over 90%. Due to this the frequency of these procedures is increasing annually and it is imperative we understand the incidence of all complication. One lesser studied complication is that of deep vein thrombosis (DVT), for which catheter ablation demonstrates all elements of Virchow"s triad. As right sided ablations are carried out to treat troublesome palpitations, not to reduce mortality, it is important all risks are identified, especially those which are themselves potentially life threatening and can be modified. Purpose To determine the incidence of DVT after right sided cardiac catheter ablation. Methods We undertook a prospective multi-center study recruiting adult patients undergoing clinically indicated cardiac ablation for atrioventricular nodal re-entrant tachycardia and atrioventricular re-entrant tachycardia with right sided accessory pathway. Important exclusion criteria included patients on anticoagulation or antiplatelet therapy. Participants underwent bilateral compression venous duplex ultrasonography from the inferior vena cava to the popliteal vein to access for DVT at 24 hours and between 10 to 14 days post-procedure. The uncannulated contralateral leg acted as a control. Result At interim analysis 71 participants had completed the study with average age 47 year (+/- 14), procedure duration 67 minutes, and with a female predominance. Seven patients developed acute DVT in either the femoral or internal iliac vein in the access leg. No thrombus was seen in the control leg. This gives an incidence of 10% (95% CI 4-19%) with p value of 0.023 on Chi-square testing. Conclusion We found a statistically significant proportion of patients undergoing right sided cardiac catheter ablation developed acute proximal DVT on ultrasound. All patients were treated with 3 to 6 months of anticoagulation therapy in accordance with NICE guidelines. These results suggest that DVT may occur at a high frequency then previously thought in this cohort and supports the consideration of peri-procedural prophylactic anticoagulation. Abstract Figure. Acute thrombus in the femoral vein

Background: Anemia is common in liver cirrhosis. This generally infers a fall in total hemoglobin mass (tHb-mass). However, hemoglobin concentration ([Hb]) may fall due to an expansion in plasma volume (PV). The "optimized carbon monoxide rebreathing method" (oCOR) measures tHb-mass directly and PV (indirectly using hematocrit). It relies upon carboxyhemoglobin (COHb) distribution throughout the entire circulation. In healthy subjects, such distribution is complete within 6-8 min. Given the altered circulatory dynamics in cirrhosis, we sought in this pilot study, to assess whether this was true in cirrhosis. The primary aim was to ascertain if the standard timings for the oCOR were applicable to patients with chronic liver disease and cirrhosis. The secondary aim was to explore the applicability of standard CO dosing methodologies to this patient population. Methods: Sixteen patients with chronic liver parenchymal disease were studied. However, tHb-mass was determined using the standard oCOR technique before elective paracentesis. Three subjects had an inadequate COHb% rise. In the remaining 13 (11 male), mean standard deviation (SD) age was 52 13.8 years, body mass 79.1 +/- 11.4 kg, height 175 +/- 6.8 cm. To these, mean +/- SD dose of carbon monoxide (CO) gas administered was 0.73 +/- 0.13 ml/kg COHb values at baseline, 6 and 8 min (and "7-min value") were compared to those at 10, 12, 15 and 20 min after CO rebreathing. Results: The "7-min value" for median COHb% (IQR) of 6.30% (6.21%-7.47%) did not differ significantly from those at subsequent time points (8 min: 6.30% (6.21%-7.47%), 10 min: 6.33% (6.00%-7.50%), 12 min: 6.33% (5.90%-7.40%), 15 min: 6.37% (5.80%-7.33%), 20 min: 6.27% (5.70%-7.20%)). Mean difference in calculated tHb-mass between minute 7 and minute 20 was only 4.1 g, or 0.6%, p = .68. No subjects reported any adverse effects. Conclusions: The oCOR method can be safely used to measure tHb-mass in patients with chronic liver disease and ascites, without adjustment of blood sample timings. Further work might refine and validate appropriate dosing regimens.

Aims Management of coagulopathy in patients with cirrhosis presenting with variceal bleeding is challenging. TEG may offer a more targeted blood product transfusion approach. This study aims to evaluate the overall impact on patient care that a TEG guided blood product transfusion strategy made on patients admitted with variceal bleeding.

Aims The aim of this audit was to determine whether there was discordance between reporting of ERCP fluoroscopic images by endoscopists and radiologists. Objectives included gauging endoscopists confidence and training at image interpretation.

Aims The aim of this survey was to assess knowledge, practice and attitudes of ERCP endoscopists towards the use of fluoroscopic X-ray radiation.

Chronic hepatitis C infection and its treatment can considerably affect patients’ health-related quality-of-life (HRQoL). This study aimed to identify and summarise the current evidence base for health state utility values (HSUVs) in patients with chronic hepatitis C infection, generated using the EuroQol 5-dimensions (EQ-5D) questionnaire.

PD-L1 is routinely assessed using immunohistochemistry (IHC) as a companion-diagnostic test. However, patients may be missing out on therapy as issues exist in determining PD-L1 positivity. This is partly due to the use of different antibodies, staining platforms and positivity cut-offs. The use of RNA in-situ hybridisation (RISH) for the detection of PD-L1 levels may be a way to address this; particularly as PD-L1 mRNA expression levels are associated with better overall survival in NSCLC. It is well established that PD-L1 expression is associated with increased numbers of Tumour Infiltrating Lymphocytes (TILs) including those which are CD8+. Therefore, it may also be worthwhile to combine PD-L1 testing with additional marker testing such as CD8. The aim of this study is to investigate the expression of PD-L1 and CD8 by RISH in a cohort of NSCLC samples and correlate with clinical outcome. RISH protocols (RNAScope® 2.5 HD assay, Advanced Cell Diagnostics, Inc.) were initially optimised on a well annotated cell line TMA (low, moderate and high expression) and compared with standard IHC (DAKO - clone 22C3). Following successful optimisation of the technique, a test cohort of 35 full-face FFPE NSCLC samples were examined for PD-L1 expression by both RISH and IHC. All slides were scored independently by a pathologist. RISH slides were scored as per ACD guidelines (0-4; based on number of positive dots per cell and number of dot clusters). IHC was scored using the standard tumour proportion score system. Image analysis (IA) was subsequently performed by Visiopharm®. Currently, a further cohort of 200 FFPE samples is being assessed, in addition to 50 FFPE samples from patients who received an anti-PD-1 therapy. Optimisation is on-going for dual CD8/PD-L1 RISH staining. In the initial 35 samples, PD-L1 was detected in 20% of cases by IHC (≥50% positivity) with mRNA expression identified in 14% of cases by RISH (≥2). In contrast with other recently published studies, issues were identified between IHC and RISH. There were 3 cases which scored positive by IHC, which were negative by RISH. Additionally, 1 case was positive by RISH but negative by IHC. The comparison between both assays produced a 'moderate agreement' as assessed using Cohen's kappa coefficient (κ=0.528, p=0.002). IA undertaken on both assays could not be statistically compared using Cohen's kappa coefficient due to the use of a composite scoring matrix to quantify RISH mRNA signals. However, IHC stained sections scored by IA showed similarity to IHC scored by a pathologist. Further optimisation is required on the RISH IA scoring algorithm. A comparison of PD-L1 IHC with RISH, combined with dual CD8/PD-L1 staining in a larger cohort of clinical samples is on-going, which will further determine the clinical utility of this technique. Data from our test cohort of samples have shown that PD-L1 detection by RISH is feasible and compares well to IHC. Preliminary data would also suggest that IA may be better than a pathologist alone, particularly in borderline cases. RISH may be a suitable method for improved detection of PD-L1 in NSCLC.

BACKGROUND & AIMS: Infections are common in patients with severe alcoholic hepatitis (SAH), but little information is available on how to predict their development or their effects on patients. Prednisolone is advocated for treatment of SAH, but can increase susceptibility to infection. We compared the effects of infection on clinical outcomes of patients treated with and without prednisolone, and identified risk factors for development of infection in SAH. METHODS: We analyzed data from 1092 patients enrolled in a double-blind placebocontrolled trial to evaluate the efficacy of treatment with prednisolone (40 mg daily) or pentoxifylline (400 mg 3 times each day) in patients with SAH. The 2 x 2 factorial design led to 547 patients receiving prednisolone; 546 were treated with pentoxifylline. The trial was conducted in the United Kingdom from January 2011 through February 2014. Data on development of infection were collected at evaluations performed at screening, baseline, weekly during admission, on discharge, and after 90 days. Patients were diagnosed with infection based on published clinical and microbiologic criteria. Risk factors for development of infection and effects on 90-day mortality were evaluated separately in patients treated with prednisolone (n = 547) and patients not treated with prednisolone (n = 545) using logistic regression. Pretreatment blood levels of bacterial DNA (bDNA) were measured in 731 patients. RESULTS: Of the 1092 patients in the study, 135 had an infection at baseline, 251 developed infections during treatment, and 89 patients developed an infection after treatment. There was no association between pentoxifylline therapy and the risk of serious infection (P =.084), infection during treatment (P =.20), or infection after treatment (P =.27). Infections classified as serious were more frequent in patients treated with prednisolone (odds ratio [ OR], 1.27; 95% confidence interval [ CI], 1.27 - 2.92; P =.002). There was no association between prednisolone therapy and infection during treatment (OR, 1.04; 95% CI, 0.78 - 1.37; P =.80). However, a higher proportion (10%) of patients receiving prednisolone developed an infection after treatment than of patients not given prednisolone (6%) (OR, 1.70; 95% CI, 1.07 - 2.69; P =-.024). Development of infection was associated with increased 90-day mortality in patients with SAH treated with prednisolone, independent of model for end-stage liver disease or Lille score (OR, 2.46; 95% CI, 1.41 - 4.30; P =.002). High circulating bDNA predicted infection that developed within 7 days of prednisolone therapy, independent of Model for End-Stage Liver Disease and white blood cell count (OR, 4.68; 95% CI, 1.80 - 12.17; P =.001). In patients who did not receive prednisolone, infection was not independently associated with 90-day mortality (OR, 0.94; 95% CI, 0.54 - 1.62; P =.82) or levels of bDNA (OR, 0.83; 95% CI, 0.39 - 1.75; P =.62). CONCLUSIONS: Patients with SAH given prednisolone are at greater risk for developing serious infections and infections after treatment than patients not given prednisolone, which may offset its therapeutic benefit. Level of circulating bDNA before treatment could identify patients at high risk of infection if given prednisolone; these data could be used to select therapies for patients with SAH. EudraCT no: 2009-013897-42; Current Controlled Trials no: ISRCTN88782125.

Aims To study the provision of paediatric liver services in a regional centre in the South of England Methods Children with liver diseases seen in paediatric Hepatology clinics over the last 5 years were included in the study. Details of demographics, underlying diagnosis, investigations and treatments were extracted in a database. Results There are two paediatric liver clinics in Southampton; one in conjunction with the supra-regional liver centre in London and the other a regional transitional clinic, with 3 consultants (supraregional, regional and transitional), dietetic, specialist nursing support and representation of the national charity Children Liver Disease Foundation in the clinics. Overall 223 children (Median Age: 12.2 years IQR: 6.8–17.1 years) were seen in the services (M:F 54.7:45.3) over the last 5 years (45 patients diagnosed/year). Children were referred from 11 hospitals across the network (Hampshire, Dorset, Wiltshire and Sussex). The most common 3 diagnoses seen in the clinics were Alpha-1-Antitrypsin deficiency (17%), Viral Hepatitides (11.7%) and Autoimmune liver disease (9.9%). With an increasing national incidence, 9.4% of the children presented with fatty liver and 15 patients with liver transplant are seen in the services. Nearly a third of patients graduated from the joint supra-regional clinic to the regional transitional clinic with provision of local radiology, bile duct stenting, bile duct botox and variceal banding services (endoscopic). Conclusions This study reflects the busy work load of a regional liver paediatric gastroenterology centre in the South of England. The paediatric liver services bridge an important gap between DGHs and supra-regional centres providing family centred specialist care for children with liver diseases, at convenience and closer to their homes. With an increasing new patient referral from DGHs and nearly third of patients transitioning to adult services, the need of a regional hepatology transitional clinic cannot be underestimated which can work in tandem with the joint supra-regional liver clinics providing uninterrupted smooth transition and continuity of care. With these increasing responsibilities, the role of a regional paediatric GI centre needs to be better recognised in managing paediatric liver patients, as currently highlighted in the NHS England specialist liver disease services contract.

The hepatocyte growth factor (HGF) receptor (MET), is frequently altered in NSCLC. Despite having a significant number of diverse mutations/alterations, randomized trials with MET inhibitors have proved disappointing, with no clinical benefit.1 More recently MET exon 14 skipping alterations have emerged as potential therapeutic targets as MET exon as they inhibit the degradation of Met, prolonging its oncogenic activity.2 Patients with Met exon 14 skipping have been found to sensitive to MET inhibitors such as crizotinib, and clinical trials of MET TKIs in METex14 mutated NSCLC are ongoing.1

BACKGROUND:Adult allogeneic haemopoietic stem cell transplant (HSCT) usually requires blood transfusion support of red cells and platelets. There are few studies describing transfusion burden after allogeneic HSCT.AIMS:This study aims to quantify and identify determinants of transfusion burden after allogeneic HSCT to improve planning, inventory management and patient counselling.METHODS:A retrospective audit of blood use (red cells and platelets) of all adult HSCT (n = 169) was performed over an 8-year period extracted from pathology and hospital databases. ABO compatibility, graft type, conditioning regimens and patient factors were analysed for up to 12 months post transplant.RESULTS:Transfusion burden was lower than expected and lower than reported by other groups. The median number of units transfused was four red cells and four platelets by day 30, and six red cells and six platelets by day 365. The median time to transfusion independence was 12 days for red cells and 16 days for platelets. Factors associated with increased red cell use included sex, disease stage, graft type (cord blood) and ABO compatibility. Disease stage and graft type (cord blood) were associated with increased platelet transfusion.CONCLUSIONS:Donor and patient characteristics are associated with transfusion burden after allogeneic HSCT. Determining transfusion burden in HSCT and identifying determinants of increased transfusion use assist in inventory planning and patient information.

Establish the potential resource and cost savings from using ePTFE covered stent-grafts configured for TIPS (SG) compared to bare metal stents (BMS). Most centres have adopted SGs to treat portal hypertension because of their reduced re-intervention rates, elimination of regular monitoring of patency and improved survival. However there is no published economic analysis identifying the related cost consequences. Understanding the improved efficiencies is essential in the current financial environment. A Markov economic model was developed to measure the incremental costs of the initial procedure and re-interventions with SG compared to BMS. Re-intervention procedures included angioplasty (67%), introducing a balloon expandable stent (22%) or a second stent (10%). The adverse events were hepatic encephalopathy and clinical relapse. Clinical data came mainly from a published RCT (Bureau 2007), whilst health care costs were from UK national databases. Compared to BMS, using SG in TIPS resulted in a cost saving of over £1,150 per patient over 2 years. Modelling 100 patients, compared to BMS, the SG cohort had 25 fewer re-interventions including angioplasties, saving 41 hours staff time in theatre and 16 inpatient days; with fewer cases of encephalopathy (16), recurrent ascites (8), variceal bleeds (5) and a markedly reduced mortality (13). The model showed that ePTFE covered stent-grafts configured for TIPS reduced mortality and re-interventions, saved theatre time and bed-days, and reduced overall costs despite the higher initial device cost.